Ethylene is a volatile plant hormone that regulates a wide spectrum of plant growth processes. For example, it is involved in the control of the plant internal hormonal balance in such processes as blocking auxin transport and inducing the synthesis of abscisic acid (ABA). Ethylene is also involved in the control of various events in the life cycle of the plant, such as hastening fruit ripening, increasing enzyme activities, acceleration of aging and senescence, dormancy, inducing chlorophyll degradation, leaf and fruit abscission, epinasty, and other changes in vegetative growth orientation, as well as root growth and altering geotropic responses. Ethylene production in the plant is augmented by various forms of environmental stresses such as high temperature, chilling and freezing, drought and excessive water or flooding, radiation, mechanical stress, and attack by pathogens or insects. Since the early years of the 20th century, ethylene has been used by growers to manipulate crops, both prior to and subsequent to harvesting. The need to control ethylene effects by either inhibiting ethylene action for such uses as prevention of pre-ripening fruit drop, decreasing fruit retention force, or applying for inducing leaf abscission in cotton as an aid to mechanical harvesting, extending fruit shelf life and the vase life of cut flowers, led scientists to attempt to develop on the one hand chemicals for blocking ethylene biosynthesis or action, and on the other hand to attempt to develop ethylene releasing chemicals. Ethephon™ is an example of an ethylene releasing chemical, commercially available by Rhône-Poulenc (hereinafter also ‘ethephon’), while aminoethoxyvinylglycine (AVG) blocks ethylene biosynthesis and the volatile compound 1-methyl-cyclopropene (1-MCP) is an antagonist of ethylene action in plants. Although 1-MCP has become very popular during the last 15 years for postharvest handling for inhibiting fruit shelf life ripening and for delaying senescence of leafy vegetables and cut flowers, its major drawback is its volatility, which restricts its use to enclosed environments. Since 1-MCP is a very effective ethylene antagonist, a major thrust of the research conducted so far has been to develop non-volatile (and, as explained in detail below, preferably water-soluble), cyclopropene derivatives.
Application of ethylene, in the form of a gas or more often by means of ethylene releasing compounds, such as Ethephon™, is mainly used to thin fruitlets, to loosen ripe fruits for facilitation of mechanical harvesting, to cause plants to shed leaves for different purposes, to induce flowering, and to accelerate ripening (banana) or color break (citrus). Ethylene is also widely used to inhibit shoot growth. On the other hand, ethylene antagonists are also quite commonly used in agriculture. Examples of uses of ethylene antagonists are prevention of abscission of various plant organs, extension of the shelf life of flowers, fruits and vegetables, and blocking or delaying leaf senescence.
In various field crops, especially cereals, grain filling is mainly determined by the rate and duration of photosynthesis in the flag leaf and the various parts of the spikes in wheat and ears in maze. The contribution of the photoassimilatory parts of the spikes or ears alone to the final grain weight has been estimated to be approximately 25%. The main factor that limits the photoassimilate supply from the flag leaf and the green ear parts is senescence. Ethylene is one of the main factors that triggers the onset of senescence. Many field crops produce ethylene naturally, particularly under conditions of stress such as drought, to which agricultural crops are often subjected. It is has been reported that application of ethylene antagonists can increase grain yield in wheat. Presumably, this effectiveness arises from the ethylene antagonists ability to delay or retard senescence, thus extending the period of time of the plant photosynthetic activity. This property of ethylene antagonists is expected to be general for all field crops, since it affects metabolic processes common to all of them.
Solubility in water usually favors the penetration of applied chemicals into plant tissues. Many plant hormones as well as synthetic hormones and hormone antagonists are poorly water-soluble acids. For preparation of aqueous solutions of these chemicals it is necessary either to first dissolve them in an organic solvent or to keep the pH near or above 7. These practices, however, are not convenient for large scale applications. A common way to facilitate the use of the above chemicals is to convert them to a salt form, which readily dissolves in water. An example for this is the rooting hormone indole-3-acetic acid. For many years nurseries have been using it as a free acid mixed in talc powder, into which the bottom of the cuttings is dipped. The observation that dipping the bottom of the cuttings into a solution of the hormone is quite often more beneficial than dipping into the free acid led to the synthesis of the highly water soluble potassium salt of indole-3-butyric acid. This product is presently favored by many nurseries than the free acid. This and other observations have stimulated research and development of water soluble ethylene antagonists based on volatile cyclopropene derivatives.
Several publications, in particular those originating from Sisler's research group in the North Carolina University, have disclosed various approaches to the synthesis of cyclopropenyl alkanoic acids. See, for example, U.S. Pat. No. 6,365,549; Tetrahedron 1996, 52, 3409; Tetrahedron 1996, 52, 12509; and Tetrahedron 2004, 60, 1803. Of the methods therein disclosed, those that would be considered a priori to be most suitable for the synthesis of cyclopropenyl-propanoic acid have been found not to succeed. Therefore, new synthetic strategies for the production of cyclopropenyl-propanoic acid are needed.
Thus, an inhibitor of plant ethylene response that is usable in field crops, and which is a solid at room temperature, has long-term stability, and is highly water soluble remains a long felt need.